Study of Rituximab Monotherapy VS Steroid Therapy on Children With New-onset Nephrotic Syndrome: A Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Recurrence-free survival time(day) after first complete remission
研究概览
简要总结
The main objective is to evaluate the effectiveness of Rituximab monotherapy versus steroid therapy on children with new-onset nephrotic syndrome within the 52-week follow-up.
详细描述
Nephrotic syndrome(NS) -------the most common glomerular disease in children. Steroid, as the mainstream therapy for decades, many patients suffer from adverse effects of it, such as growth impacted, fat, and glaucoma.There is a urgent need for Steroid-sparing therapy. Rituximab, as a chemical monoclonal antibody against the cluster of differentiation antigen 20(CD20), has proved to be effective in patients with frequent-relapse/steroid-dependent NS. It has also been reported to be effective in six adult patients with new-onset NS. Rituximab mono-therapy in new-onset pediatric NS patients is still unclear.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New-onset idiopathic nephrotic syndrome
- •Glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
排除标准
- •Glomerular hematuria: Urine red blood cell counts≥ 10/high power field(HP), ≥ 3 times within 2 weeks;
- •Continuous hypocomplementaemia(< 0.9g/L) ;
- •Repeated or persistent Hypertension(systolic and/or diastolic blood pressures measured greater than the 95th percent of blood pressure in children matching sex, age and height ≥3 different time points)
- •Diagnosis of secondary NS, such as secondary to Systemic Lupus Erythematosus, Immunoglobulin A Vasculitis(IgAV), diabetes, Hepatitis B virus(HBV) infection, etc.
- •Complicated with other kidney diseases, such as multiple renal cysts, ANCA vasculitis, urinary system abnormalities, etc;
- •With a family history of nephrotic syndrome, chronic glomerulonephritis, uremia, or other kidney diseases;
- •Other monogenic genetic diseases known as the effect the condition of nephrotic syndromes, such as Wilms' tumor 1(WT1), NPHS2, LAMB2, PLCE1, etc.
- •Congenital or acquired immunodeficiency, or patients with active tuberculosis, active Epstein-Barr virus and cytomegalovirus(CMV), acute hepatitis B, hepatitis C, HIV infection, deep fungal infection or other active infections.
- •Laboratory indicators were abnormal, such as moderate or severe neutropenia(≤1000/μL)， moderate or severe anemia(hemoglobin<9.0g/dL), Thrombocytopenia (platelet count<100* 10^12/L) or with abnormal hepatic function (Alaninetransaminase(ALT), aspartate Aminotransferase(AST) or bilirubin >2.5*upper limit of normal value and continue to increase for 2 weeks);
- •Steroid or immunosuppressive medicine for other diseases within 3 months, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, tripterygium wilfordii, etc.
- •With tumor, severe cardiac failure, severe hepatologic diseases, hematological diseases, or other severe system diseases.
- •Patients who are known to be allergic to rituximab;
- •History of transplantation, excluding cornea or hair transplantation;
- •The attenuated live vaccine was inoculated within 1 month before enrollment;
- •Patients who participated in other clinical trials within three months before enrollment;
- •Patients are not suitable for inclusion in the trial by any investigator.
研究组 & 干预措施
Rituximab Group
Rituximab dose: 4 doses of 375 mg/m2 rituximab at 1-week intervals( within +7 days).
干预措施: Rituximab (Drug)
Steroid Group
Daily oral prednisone/prednisolone 2 mg/kg/d (maximum 60 mg/d) for 6 weeks followed by alternate day prednisone/prednisolone, 1.5 mg/kg (maximum of 50 mg), for other 6 weeks.
干预措施: Steroid (Drug)
结局指标
主要结局
Recurrence-free survival time(day) after first complete remission
时间窗: From complete remission to 52 weeks
The time from complete remission to the first relapse during the whole 52-week follow-up in patients who achieve complete remission within 6 weeks. In order to evaluate the remission, all the participants will document their proteinuria. Relapse is defined by first-morning urine dipstick ≥3+ on three or more consecutive days, 24-h PCR≥2.0g/g, or 24-h urine protein ≥ 50mg/kg, with or without edema after complete remission(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases). Complete remission is defined by the first morning or 24h PCR ≤ 0.2g/g (or negative or trace dipstick) on three or more consecutive occasions(KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases).
次要结局
- Complete remission of nephrotic syndrome(From admission day to 6 weeks)
- Inefficiency of nephrotic syndrome(From admission day to 6 weeks)
- Relapse of nephrotic syndrome(From admission day to 52 weeks)
- Cumulative prednisone dosage of each individual (milligrams per kilogram per year)(From admission day to 52 weeks)
- The time(day) to first complete remission(From admission day to 6 weeks)
研究者
Mao Jianhua
Associate Dean
The Children's Hospital of Zhejiang University School of Medicine